Differentiation of primary MCF-7 from drug resistant MCF-7/ADR by BMVC molecule

• Main Authors: Chiung-Wen Kouh, 郭瓊文
• Other Authors: Ta-Chau Chang
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/68521596033068740692

碩士 === 國立陽明大學 === 生醫光電研究所 === 100 === Anticancer drugs are developed to effectively target to the cancer cells for most of malignant solid tumor chemotherapy. However, there are some tumors having the ability to exhibit simultaneous resistance to a number of anticancer drugs. This multidrug resistance (MDR) has become a major problem in cancer chemotherapy. In addition to develop anticancer drugs for overcoming the drug resistance, it is also an important issue to point out the cellular difference between drug sensitive cancer cells and drug resistant cancer cells. Here we combine a fluorescence probe 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) molecule which has designed and synthesized in our laboratory. The previous studies showed that BMVC is able to distinguish cancer cells from normal cells based on its fluorescence; more bright fluorescence in the nucleus of cancer cells, while weaker fluorescence in the cytoplasm of normal cells. Moreover, the lysosomal membrane permeability plays an important role in regulating the localization of BMVC. Accordingly, we propose to use this small molecule in examining the difference between drug sensitive cancer cell and drug resistant cancer cell. We have investigated the breast cancer cell, MCF-7, as a drug sensitive cancer cell and its P-glycoprotein MDR subclone, MCF-7/ADR. The distinct BMVC fluorescence allows us to explore different cellular response based on the interaction of BMVC to MCF-7 and MCF-7/ADR cells. Here we first discuss the mechanism of different distribution of BMVC in MCF-7 and MCF-7/ADR cells. Although the overexpression of P-glycoprotein is a major reason for the multidrug resistance, our results show that P-glycoprotein has little effect to BMVC with respect to Doxorubicin. Again, BMVC study reveals that lysosomal membrane permeability is different between MCF-7 and MCF-7/ADR cells. We have further used BMVC derivatives to examine the relationship of hydrogen bonding capacity (HBC) to lysosomal membrane permeability for drug design.